Asthma is a prevalent pulmonary disease that affects more than 300 million people worldwide and imposes a substantial economic burden. While medication can effectively control symptoms in some patients, severe asthma attacks, driven by airway inflammation induced by environmental and infectious exposures, continue to be a major cause of asthma-related mortality. Heterogeneous phenotypes of asthma include type 2 (T2) and non-T2 asthma. Non-T2 asthma is often observed in patients with severe and/or steroid-resistant asthma. This review covers the molecular mechanisms, clinical phenotypes, causes and promising treatments of non-T2 severe asthma. Specifically, we discuss the signalling pathways for non-T2 asthma including the activation of inflammasomes, interferon responses and interleukin-17 pathways, and their contributions to the subtypes, progression and severity of non-T2 asthma. Understanding the molecular mechanisms and genetic determinants underlying non-T2 asthma could form the basis for precision medicine in severe asthma treatment.

哮喘是一种普遍的肺部疾病，影响着全球超过 3 亿人，并造成了巨大的经济负担。虽然药物可以有效控制一些患者的症状，但由环境和感染暴露引起的气道炎症驱动的严重哮喘发作仍然是哮喘相关死亡的主要原因。哮喘的异质性表型包括 2 型 （T2） 和非 T2 型哮喘。非 T2 哮喘常见于严重和/或类固醇耐药性哮喘患者。本综述涵盖了非 T2 重度哮喘的分子机制、临床表型、原因和有前景的治疗方法。具体来说，我们讨论了非 T2 哮喘的信号通路，包括炎性小体的激活、干扰素反应和白细胞介素 17 通路，以及它们对非 T2 哮喘亚型、进展和严重程度的贡献。了解非 T2 哮喘的分子机制和遗传决定因素可以构成严重哮喘治疗精准医疗的基础。